Fig 1: Activating GLP-1R suppresses exogenous lactate-induced NLRP3 inflammasome activation and histone lactylation in fibroblasts. a and b Fibroblasts were transfected with NC siRNA or NLRP3 siRNA followed by exogenous lactate (20 mM) treatment for 24 h. The protein levels of collagen I, ASC and caspase-1 p20 were assessed by western blotting (a, n = 4). The concentration of IL-1β in the supernatant were measured by ELISA (b, n = 4). c-j Fibroblasts were pretreated with liraglutide (1000 nM) for 1 h, followed by exogenous lactate (20 mM) treatment for 24 h. The intracellular lactate production was measured (c, n = 6). The protein levels of collagen I, PFKFB3, NLRP3, ASC and caspase-1 p20 were measured by western blotting (d and e, n = 4–5). The immunofluorescence staining for ASC specks in fibroblasts was performed. The white arrows indicated ASC speck formation in fibroblasts. Scale bar = 50 μm (f). The concentrations of IL-1β and IL-18 in the supernatant were measured by ELISA (g, n = 4). Western blotting was performed to assess the protein levels of H3K18la, H4K12la and p300 (h, n = 4–5). ChIP‒qPCR was performed to determine the enrichment of H3K18la at the promoter regions of Acta2 and Col1a1 (i, n = 5). The transcription of α-SMA and collagen I was quantified by qRT‒PCR (j, n = 5). Data are presented as mean ± SD. *P < 0.05, **P < 0.01, and ***P < 0.001. Lir, liraglutide; Lac, lactate